General Discussion

Sinonasal undifferentiated carcinoma (SNUC) is a rare cancer of the nasal cavity and/or paranasal sinuses. Initial symptoms range from bloody nose, runny nose, double vision, and bulging eye to chronic infections and nasal obstruction. It has been associated with several types of papilloma in the nasal cavity, which are benign, but can give rise to malignancy. Prior irradiation for other cancers has been associated with the development of SNUC in a number of cases, and has been associated with a genetic mutation known to be associated with cancer development. Most patients have not had prior irradiation, and no other causes have demonstrated to be significant, though some studies have found that woodworkers and nickel factory workers are generally more susceptible to sinonasal malignancy of all types.

Signs & Symptoms

Causes

The nasal cavity lies just behind the nostrils and continues backward to the nasopharynx, a space just behind the nasal cavity that is contiguous with the oropharynx (the space just behind the mouth and oral cavity). The paranasal sinuses are these: the maxillary sinus under the eyes, the ethmoid and sphenoid sinuses, which are above and behind the nasal cavity, and the frontal sinuses, which lie behind the space between the eyebrows. The nasal cavity and paranasal sinuses are lined with a thin layer of tissue called Schneiderian epithelium, which has cilia, which are tiny hairs whose movements aid in pushing dirt and other contaminants out of the nasal cavity.

Schneiderian epithelium gives rise to several types of papillomas, a type of benign tumor, several of which are known to give rise to cancers. The rare case of SNUC is known to arise in these papillomas. The precise localization of the Schneiderian epithelium to the nasal cavity and paranasal sinuses explains both the strict localization of this tumor, and the unique and troublesome combination of symptoms that make SNUC a difficult disease.

In the original scientific paper on SNUC, seven of eight patients were smokers, and the eighth had significant occupational exposure to known carcinogens in both coal mines and chrome plating factories (13). These patients came from a wide geographical distribution, which seemed to rule out environmental factors. Several later papers failed to confirm the data on smoking as a potential cause of SNUC. A large study from Wales, Canada and Norway has presented substantial evidence that nickel refinery workers are susceptible to all sinonasal cancers with incidences of individual pathologies proportional to those in the general population, as opposed to the established association of adenocarcinoma specifically with wood workers (59)(60). However, the majority of SNUC patients are not nickel workers, so other factors as yet undefined are at work in SNUC.

Retinoblastoma is a rare childhood tumor that arises in one of the layers of the eye. Treatment usually involves removal of the eye, and sometimes radiation therapy. There have been several cases of patients with retinoblastoma who have been treated with radiation and have gone on to develop SNUC many years later. In genetic studies done on several of these patients, mutations in a gene known as the retinoblastoma gene (on chromosome 13, and designated RB-1) have been found. This gene is known to stop the progression of healthy cells into cancer cells by controlling the cell division cycle, so a mutation increases the likelihood that cells will become cancerous. However, this, too, accounts for only a small number of SNUC patients.

Epstein Barr virus (EBV) is a human herpes virus with the known ability to cause cancer. In the nasopharynx, which is adjacent to the nasal cavity as discussed above, EBV is known to give rise to nasopharyngeal carcinoma (NPC), and in the sinonasal region it gives rise to PSNPC. It has been fairly well established that SNUC is not caused by EBV, but some controversy over this may still exist.

The bottom line is that the cause of SNUC is still undetermined.

Affected Populations

There is no regional predilection for SNUC. It affects people in all countries more or less equally, based on available evidence. There is approximately a 2:1 male:female prevalence, and the average age from available published studies is 53 years old. The age range is 14 to 83 years old.

Related Disorders

Olfactory neuroblastoma is a malignant tumor of the sinuses and adjacent areas of the nose (sinonasal region) that affects mainly adults and affects both sexes equally. Nasal obstruction and nosebleeds (epitaxis) are the most common symptoms. The tumor is described as locally aggressive but distant metastases occur in about 20% of cases, mainly to lymph nodes and lung. The malignancy is usually treated by surgery supplemented by radiotherapy and chemotherapy.

Sinonasal neuroendocrine carcinoma (SNEC) is a very rare malignancy that is often overlooked because it is very difficult to diagnose accurately. The nasal cavity is the most common location. There appears to be a greater propensity for men than for women to acquire this disorder.

Primary sinonasal nasopharyngeal-type undifferentiated carcinoma (PSNPC) is an even more rare tumor than any of the above. Both PSNPC and SNUC have been reported to be associated with Epstein-Barr virus (EBV) but the two are considered two different entities.

Inverted and oncocytic papillomas are two of several types of papillomas that vary in histologic appearance. The identification of the type of papilloma is important because inverted and oncocytic papillomas are associated with the development of particularly aggressive squamous cell carcinomas. Papillomas are not uncommon, presenting in adults between 30 and 50 years of age. Men are affected twice as often as women. Nasal obstruction is the most common presenting symptom. Local excision may lead to local recurrence in 50-70% of cases, usually within 1-2 years. The recurrence does not appear to be dependent upon the histology. The length of time between recurrences is not apparently related to the risk of subsequent cancer. Human papilloma virus (HPV) has been identified in inverted papillomas.

Standard Therapies

The diagnosis of SNUC requires two things: a history of a mass in the nasal cavity or the sinonasal region (see symptom section above), and tissue obtained via surgery or biopsy. Neither imaging studies nor laboratory studies are required, but sometimes SNUC does not manifest itself until imaging studies are performed for other sinus problems.

Treatment

The treatment of SNUC has no firmly established protocol. What has been established is that the disease tends to recur in the same area from which it arises, and that treatment must focus on eliminating the disease via all available treatment modalities. This means the ideal treatment is a coordinated effort by a team of medical oncologists, radiation oncologists, and surgeons who are specially trained to deal with cancers that occur in this very challenging anatomical region. Treatment, therefore, involves chemotherapy, radiation therapy and surgery in some combination. Follow-up treatment can involve dental prostheses, eye prostheses, and visits with dentists and ophthalmologists, in addition to regular follow-up with the original treating doctors for cancer follow-up. This follow-up consists of regular magnetic resonance imaging (MRI) and, if necessary, tissue biopsy.

Investigational Therapies

Though research on cancer generally is ongoing, research on SNUC is virtually non-existent. The treatment paradigm for SNUC is drawn from successful treatment of other malignancies, and its rarity makes it unlikely ever to be studied in any great depth. In the near future, as the National Cancer Institute (NCI) builds an expanded database of information for all tumor types, there may be hope for as yet unconceived treatments.

Treatments that are highly specific to individual tumor types have resulted from just this sort of highly specific information about the types of receptors that appear on the surface of tumor cells. These receptors are used by the tumor cells to manipulate growth factors that are normally found within the body to their advantage. Three of these drugs are Herceptin, epidermal growth factor receptor blocker (EGFR blocker), and Gleevec. While these drugs were developed in the context of specific tumors (breast cancer and chronic myelogenous leukemia especially), recent discoveries have shown that other tumor types express these receptors, and thus may be susceptible to these drugs.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

McCary SW, Levine PA, Cantrell RW: Preservation of the Eye in the Treatment of Sinonasal Malignant Neoplasms With Orbital Involvement: A confirmation of the original treatise. Archives of Otolaryngology Head and Neck Surgery 122: 657-659, 1996.

Mills SE: Neuroendocrine Tumors of the Head and Neck: A Selected Review with Emphasis on Terminology. Endocrine Pathology 7(4): 329-343, 1996.

Years Published

2004

The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.

The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.

NORD's Rare Disease Database provides brief introductions for patients and their families to more than 1,200 rare diseases. This is not a comprehensive database since there are nearly 7,000 diseases considered rare in the U.S. We add new topics as we are able to do so, with the help of rare disease medical experts.

If you are seeking information about a rare disease that is not in this database, we would suggest contacting the Genetic and Rare Diseases Information Center (GARD) at the National Institutes of Health. NIH has the most complete database of rare diseases in the U.S.

Representatives of patient organizations whose medical advisors are interested in assisting NORD in creating a report on a disease not currently covered in this database may write to orphan@rarediseases.org.